The University of Massachusetts Amherst is requesting funds from NIH/NCRR through the Shared Instrumentation Grant program to purchase a Thermo Scientific LTQ Orbitrap Elite, high-resolution hybrid FT mass spectrometer with ETD and HCD capabilities for protein research. This instrument will support the research of sixteen NIH-funded investigators at the University of Massachusetts Amherst from the Departments of Biochemistry & Molecular Biology, Chemistry, Veterinary & Animal Sciences and Biology, as well as clinical faculty at the associated Pioneer Valley Life Sciences Institute (PVLSI). Research requiring the Orbitrap includes projects investigating protein misfolding diseases, protein folding in the cell, and research involved in developing anti-cancer therapeutic strategies. Liquid chromatography separation of protein proteolytic digests coupled to the high sensitivity, accuracy and speed of tandem mass spectrometry achieved by the Orbitrap, are critical capabilities required by NIH-funded projects. High-resolution mass measurements are necessary for unambiguous identification of peptides in complex mixtures, and particularly for assignment of cross-linked or modified peptides. These capabilities are key to the success of projects described in this proposal. All of the major users of the requested instrument currently use the UMass Amherst Mass Spectrometry Center for routine analyses, but now have need for the enhanced accuracy and rapid data acquisition of the Orbitrap. Currently no instrument with the necessary capabilities and features of the requested instrument is available on campus or in the local geographic area. Thus, research progress is limited by instrumentation available in the Center and/or the need for external collaborations or outsourcing. These limitations are increasing the cost and time involved in obtaining data and preventing the development of new research approaches and acquisition of critical data. The requested instrument will bring the following capabilities to campus: high sensitivity mass spectrometric detection, high resolution and high mass accuracy for confident compound identification, rapid spectral scanning compatible with liquid chromatography separation of complex mixtures, and novel fragmentation capabilities needed for secondary identification and confirmation of chemical structures. The instrument will be housed in the New Life Sciences Building, with many of the major instrument users, thus providing convenience of proximity combined with bringing together researchers with diverse interests via a collective analytical tool. The instrument will be incorporated into te UMass Amherst Mass Spectrometry Center, which is directed by the PI and employs a full time PhD staff scientist. The Orbitrap will be not only an invaluable research tool, but will also be employed in educating undergraduate and graduate level students in the expanding field of mass spectrometric analysis of proteins.